title: Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.
abstract: BACKGROUND
  The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic magnetic resonance imaging (MRI) were correlated with histopathologic grade in mammary soft tissue tumors.
  
  
  METHODS
  A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N -ethyl-N -nitrosourea (ENU), a potent carcinogen. Dynamic contrast-enhanced MRI was performed using a small-molecular contrast medium [gadopentetate, MW = 0.5 kDa] and a macromolecular contrast medium [albumin-(Gd-DTPA)30, MW = 92 kDa] at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (KPS), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bi-directional kinetic model. MRI microvascular characteristics were correlated with histopathologic tumor grade.
  
  
  RESULTS
  Tumor permeability to macromolecular contrast medium, characterized by KPS, showed a highly positive correlation with tumor grade (r 2 = 0.76, P < 10(-10)). KPS values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r 2 = 0.25, P < 0.003). No correlation between KPS or fPV values and tumor grade was found using gadopentetate (r 2 = 0.01, P > 0.95 and r2 = 0.03, P > 0.15, respectively).
  
  
  CONCLUSIONS
  Quantitative tumor microvascular permeability assays generated with macromolecular MRI contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.
authors.affiliation: Department of Radiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0628, USA.
authors.forename: H
authors.initials: H
authors.lastname: Daldrup
authors.forename: D M
authors.initials: DM
authors.lastname: Shames
authors.forename: M
authors.initials: M
authors.lastname: Wendland
authors.forename: Y
authors.initials: Y
authors.lastname: Okuhata
authors.forename: T M
authors.initials: TM
authors.lastname: Link
authors.forename: W
authors.initials: W
authors.lastname: Rosenau
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: R C
authors.initials: RC
authors.lastname: Brasch
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D002199:Capillary Permeability; D003287:Contrast Media / Q000493:pharmacokinetics*; D005038:Ethylnitrosourea; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D016014:Linear Models; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D015674:Mammary Neoplasms, Animal / Q000098:blood supply* / Q000139:chemically induced / Q000145:classification / Q000473:pathology*; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
chemical_list: D000418:Albumins; D003287:Contrast Media; D046911:Macromolecular Substances; D019786:Gadolinium DTPA; D005038:Ethylnitrosourea